ABSTRACT The tripartite motif (TRIM) family of E3 ubiquitin ligases is known to play a crucial role in the initiation, growth, and metastasis of various tumors. However, little is known about the biological features and relevant molecular mechanism of Tripartite motif‐containing 63 (TRIM 63) in melanoma. The expression levels of TRIM63 and purinergic receptor P2Y1 (P2RY1) in melanoma were examined by online database. Cell counting kit‐8 (CCK‐8) and colony formation assay were carried out to explore the effects of TRIM63 on melanoma cells proliferation. Transwell assay was used to explore the influence of TRIM63 on melanoma cells invasion and migration. Bioinformatics, co‐immunoprecipitation (co‐IP) assay, ubiquitination assay, and protein stability assay were used to detect the regulatory mechanism of TRIM63 on P2RY1. TRIM63 was upregulated in melanoma samples, and a higher expression level of TRIM63 indicated a shorter overall survival of melanoma patients. Knocked down of TRIM63 obviously suppressed the proliferation, invasion, and migration abilities of melanoma cells. Mechanistically, TRIM63 was regarded as a posttranslational mediator of P2RY1, and TRIM63 was co‐immunoprecipitated with P2RY1 and degraded its protein level. Notably, silencing P2RY1 alleviated melanoma cells progression by TRIM63 depletion. Collectively, these data suggested that TRIM63 contributed to melanoma cells growth and mobility by ubiquitination of P2RY1 and may be a promising candidate as a potential diagnostic and therapeutic marker for patients with melanoma.
Zhang et al. (Thu,) studied this question.